Fv-1 locus has been recognized as an important host genetic factor for controlling viral leukemogenesis in mice. Previous studies have established the basic characteristics of the Fv-1 restriction, which includes the dominant expression of Fv-1 alleles respectively against N- and B-tropic viruses, general distribution of this locus in the mouse species, intracellular restriction event, presence of specific cellular gene products, presence of virion targets and virus-caused abrogation of the restriction mechanism. Various biochemical evidences have implied that Fv-1 restriction results in impaired viral gene integration and that formation of viral closed circular supercoiled DNAs is specifically blocked. Based on current knowledge of reverse transcription and our recent experimental results, a working model is constructed in which we postulate that the "target molecules" play a critical role in the enzymatic synthesis of large terminal repeated sequences of viral DNA and that Fv-1 gene products interfere with this synthesis by binding to the target molecules. Based on the working hypothesis, experimental approaches are planned: (a) to determine by genetic analysis whether or not ability to depress the synthesis of viral linear DNA is the property of certain Fv-1n alleles; (b) to elucidate by the restriction endonuclease mapping/the recombinant DNA cloning/the DNA sequencing techniques the possible structure alterations in viral DNAs isolated from Fv-1 restrictive cells; (c) to establish in vitro reverse transcription of N- and B-tropic viruses for characterization of Fv-1 gene products and other cellular factors; and (d) to study viral RNA-protein and DNA-protein complexes in Fv-1 permissive and restrictive cells early after infection. The proposed work has the purpose not only to understand the molecular mechanism of Fv-1 restriction but also to use Fv-1 locus as a model system for studying how host genetic factors may control the synthesis of transposable gene elements in mammalian organisms.